Evaluating Evidence and Membership Benefits

Hey everyone, welcome to a sneak peek Ask Me Anything or AMA episode of the Drive podcast. I'm your host, Peter Ata. At the end of this short episode, I'll explain how you can access the AMA episodes in full, along with a ton of other membership benefits we've created Or you can learn more now by going to PeterataMd. com forward slash subscribe So without further delay, here's today's sneak peek of the Ask Me Anything episode Welcome to Ask M Anything, AMA episode eighty five. Today we're talking about medications and supplements. This is one of the topics I get asked about more than almost anything else, and I think it's also one of the easiest areas to go wrong. People tend to ask me whether something is good or bad, whether they should take it or not. But those are I think kind of the wrong questions. The right question is whether a specific intervention makes sense for a specific person with a specific problem That's what I'm going to try to get to today. So in this episode, we'll co Why defining the problem matters more than picking the intervention different jobs a medication or supplement can do and why the evidence bar should move depending on the job How to tell strong evidence from weak evidence and why mechanism alone isn't enough why baseline risk changes everything and how relative risk can mislead you How to think about the real downside of taking something Side effects, yes, but also cost, hassle and opportunity cost. How to determine whether the supplement you're taking is having any real effect how to stop taking something Wh supplements specifically deserve a lot more skepticism than people give them. And finally a short list of over the counter supplements that I think are probably worth the risk reward trade off So without further delay, I hope you enjoy AMA number eighty five Peter, welcome to another AMA. How you doing? Very well, thanks We will get right into it today on AMA all around medications and supplements. First question Before someone takes any medication or supplement How do you think that they should define what the problem is in a way that increases the odds that they look for and pick interventions that actually benefit them and reduce risk. opposed to best waste money and at worse cause other harm that they don't know about You know, I think this is actually one of the biggest challenges fromom a sort of mental model standpoint is plaguing most people when they think about supplements in particular, but I think also frankly, pharmaceuticals. People are I think typically defining the problem at the wrong level of abstraction. So they'll say things like I want to be healthier or I want more energy or I want to pursue better longevity The challenge is that those are not really actionable problem definitions. They're vague, difficult to measure, very difficult to falsify and things like that. So I would suggest that we reframe this discussion around what would be actionable metrics or actionable parts, right? So one would be a metric that can be studied, two would be a threshold against which you would measure. And then I think a third potential one would be a time horizon What am I measuring? What level tells me that there's a problem and by extension, a solution? And when do I expect that to happen And so if you can't come up a priority with some sense of those things, you're probably not in a good spot to start anything For example, let's use a tangible example. inststead of saying my cholesterol is bad You would say my AOB is one hundred and thirty milligrams per deceliter. I want to get it below sixty milligrams per deceliter and I'd like to do that in the next six months. Instead of saying, you know, my sleep is bad, you might say, it takes me sixty minutes to fall asleep on you know, four or five nights a week And I want to make that under ten minutes to fall asleep within two months. That's a real problem definition The next question is the counterfactual. What happens if I do nothing? Does this problem meaningfully increase risk, reduce quality of life or create some downstream consequence? I think this question is important because it separates real problems from things that merely you know feel actionable And it matters because Pure problem definition almost guarantees some sort of false positive. So if the problem is vague, almost anything can look like it helps. You sleep a little better one week, yourour energy is a little better on Tuesday, O lab improves a little, and now you're telling yourself a story. And we all do this. I mean, that's we're storytelling machines And I think that's how people end up taking things for years without ever knowing if they've solved anything real So I think the rule here could be pretty simple, right? Do not start with the molecule, Start with the problem define tightly enough that you could actually be proven wrong So if you can't state the metric, the threshold and the timeline and even the consequences of doing nothing, You're not really making an intervention decision. you're probably impulse shopping on, you know, your favorite website And when looking at different medications and supplements How do you think about and maybe classify the quote unquote job that they would do and based on that classification Does it change the evidence threshold you like to see and how much risk you're willing to tolerate? Once the problem is defined, I think the next question is asking, okay, what is the purpose of that intervention And again, it matters because it requires different standards. So if you don't classify this job as you describe it correctly, you're very likely going to apply the wrong evidence threshold and accept the wrong amount of risk So I think we could put these into four buckets Diseease treatment Symptom relief risk reduction and I hate the term, but I think we just need to use it and it's optimization So They might sound sort of similar on the surface, but they're actually quite different. So if the quote unquote job is disease treatment The bar is high, right? Does this improve the disease in a meaningful way And of course, here, you would be willing to accept more downside because the underlying problem is serious And the counterfactual is strong. presresumably if you have a disease and you do nothing, the disease will get significantly worse But at the same time, you're going to want stronger evidence, ideally hard outcome trials, or at least some well validated surrogate endpoint, not just a compelling story Now if the job is symptom relief The question is a bit different. Does the person actually feel or function better. And here we're dealing with something that's subjective You may be willing to frankly tolerate placebo risk because if the symptoms meaningfully improve and the downside is low, that could still be a reasonable trade off If the job is risk reduction, you're treating something that a person can't feel, almost by definition. So the evidence bar again here needs to be pretty high. That usually means hard outcomes when available Or again, at least a very validated surrogate marker And again, not all biomarkers are equal here. AO B is a very well validated surrogate biomarker whereereas, you know, some vague inflammatory marker or heavy metal is not necessarily going to be in that category as you're you know someomeone's pontificating about detoxifications or something like that If the job is optimization, then I think skepticism should go up, right? This is where error rates are highest. The person is usually starting from a relatively healthy baseline And the expected effect is often small. The claims are usually made in a mechanistic way And there's generally no objective way to determine whether supplement or medication is benefiting you making your ability to basically fool yourself enormous. So I think the challenge and probably the reason we're even doing this episode is in part because most of the longevity interventions are really optimizations, masquerading as risk reductions. They kind of borrow the language of prevention, aging, health span, resilience, longevity But the actual evidence that they put forth looks much more like speculative optimization interventions rather than true risk reduction And I think this distinction really matters, right? This classification should change both your evidence threshold and your risk tolerance I think the more serious and concrete the problem, the more downside you may be willing to keep, as I said, and the more speculative the gold, the less downside you should be willing to tolerate So I guess to summarize that, if you're looking at disease treatment, you want to demand strong evidence, but you'll accept more risk. If you're looking at symptom relief You prioritize the actual lived benefit, but watch for placebo and noise and factor in the unknowns about safety Risk reduction, you're going to have to look at validated surrogates or hard outcomes, although the latter tends to be challenging And if it's about optimization, you're going to default into a skeptical state especially around safety So Peter, let's double click on one of the things you briefly mentioned there, which is kind of evidence when looking at medications and supplements. So When people are evaluating how they're thinking about a medication supplement for themselves What are common ways that you see people confuse the different tiers of evidence and How can people prevent that in practice? So how can people be a little bit more aware? So when they're looking at various claims they start to understand how good those claims are. Thank you for listening to today's sneak peek AMA episode of The Drive. 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